Single-Islet Proteomics Maps Pseudo-Temporal Islet Immune Responses and Dysfunction in Stage 1 Type 1 Diabetes.

ABSTRACT: Progressive β-cell dysfunction precedes the onset of type 1 diabetes (T1D), yet the molecular mechanisms driving early T1D development remain poorly understood. Although single-cell RNA-sequencing has uncovered transcript-level changes in human islet cells, it offers limited insight into the heterogeneity of distinct islet microenvironments. Here, we applied a single-islet proteomics workflow to profile intra-donor islet heterogeneity in three stage 1 T1D cases with matched non-diabetic controls and define in situ protein signatures of pseudo-temporal islet dysfunction. Intra-donor analyses of ~100 individual islets per donor revealed highly consistent proteomic patterns reflecting pseudo-time progression of islet immune responses and β-cell dysfunction. Several pathways, including extrace

SUBMITTER: Kelly S 

PROVIDER: S-EPMC12642322 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature